Campus Units

Animal Science, Chemistry, Veterinary Diagnostic and Production Animal Medicine

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

10-2017

Journal or Book Title

Antiviral Research

Volume

146

First Page

28

Last Page

35

DOI

10.1016/j.antiviral.2017.08.006

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiological agent of PRRS, an economically significant disease of swine worldwide. PRRSV is poorly controlled by the currently available vaccines, and alternative control strategies are needed to help prevent the continual circulation of the virus. Previously, we developed a synthetic route for the natural compound atractylodinol and demonstrated anti-PRRSV activity in vitro. However, the synthetic route was inefficient and the yield was poor. To identify PRRSV inhibitors that could be synthesized easily and cost-effectively, we synthesized a series of atractylodinol analogs and characterized their anti-PRRSV activity in vitro. A furan-substituted bis-enyne subunit was found to be critical for PRRSV inhibition. Six analogs had potent inhibitory activity against PRRSV with 50% inhibition concentration (IC50) of 0.4–1.4 μM and 50% cytotoxic concentration (CC50) of 209–1537 μM in MARC-145 cells. Three of the most promising compounds also demonstrated significant antiviral activity and low cytotoxicity in porcine macrophages. Inhibition of PRRSV in MARC-145 cells occurred primarily at a post-entry step during PRRSV replication, between 4 and 12 h post-entry. These results suggest that atractylodinol analogs are promising antiviral candidates that could augment current PRRSV control strategies.

Comments

This is a manuscript of an article published as Evans, Alyssa B., Pengfei Dong, Hyelee Loyd, Jianqiang Zhang, George A. Kraus, and Susan Carpenter. "Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus." Antiviral Research (2017). doi: 10.1016/j.antiviral.2017.08.006. Posted with permission.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Copyright Owner

Elsevier Ltd.

Language

en

File Format

application/pdf

Available for download on Monday, October 01, 2018

Published Version

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